First lines of therapy for hematological malignancies generally include chemotherapy and/or chemo-immunotherapy with monoclonal antibodies. However, some patients experience relapse or progression of the disease and become sometimes refractory to standard treatment.
Immune therapy including allogenic stem cell transplantation (SCT) represents an alternative way for therapy in these patients who are difficult to cure or less likely to be cured with standard chemotherapy. Hematopoietic stem cell transplantation (HSCT) is a therapy that involves taking hematopoietic stem cells from a donor or from cord blood and infusing them intravenously to the recipient conditioned to accept the transplant. However, the overall survival rate after transplantation is still only of 40% to 60% due to severe posttransplant complications including graft versus host disease (GVHD). GVHD is a generic name for diseases that are caused by the immune reaction of transferred or transplanted immunocompetent cells (e.g., mature T cells) against host tissues and that can induce severe organ toxicity leading to death in some cases.
Therefore, human leukocyte antigen (HLA) matching is essential to reduce the risk of graft rejection and GVHD. However, non-HLA genes also impact on transplant outcome and GVHD can be fatal even in patients receiving transplants from HLA-identical matched sibling donors (MSD). Furthermore, MSD are only available for about one third of the patients and, therefore, alternative donors are needed. HLA-matched unrelated donors (MUD) are more widely used than cord blood or mismatched related donors but the risk of GVHD must also be taken in consideration for patients receiving transplants from MUD.
Accordingly, there is still a need for methods useful for predicting the risk of developing GVHD in patients receiving transplants (or conversely methods for determining whether a candidate donor is at risk of inducing GVHD in a recipient).
Recently, two retrospective studies have demonstrated the clinical relevance of invariant NKT (iNKT) cells in the prediction of acute graft versus host disease (aGVHD) by analyzing the frequency distribution of effector and regulatory lymphocytes in peripheral blood stem cell (PBSC) of recipients of allogeneic HSCT (Rubio et al., Blood 2012) or of donor grafts (Chaidos et al., 2012). An impaired reconstitution of iNKT cells in the recipients or a low CD4− iNKT cell dose in the graft were shown to represent independent parameters that can significantly predict the occurrence of aGVHD after HSCT.
However, a method predicting the risk of developing aGVHD based on the direct determination in blood or graft samples of iNKT cells is not satisfying for physicians since the threshold between low and high iNKT cells is difficult to determine leading for instance to a risk of error for intermediate results.